chr17-50582482-A-G

Variant names:

• chr17-50582482-A-G
• rs198555
• NM_018896.5:c.2301+3918A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018896.5(CACNA1G):​c.2301+3918A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 152,002 control chromosomes in the GnomAD database, including 26,232 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (26232 hom., cov: 31)
• Consequence: CACNA1G NM_018896.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.746
• Publications: 3 publications found

Genes affected

CACNA1G (HGNC:1394): (calcium voltage-gated channel subunit alpha1 G) Voltage-sensitive calcium channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division, and cell death. This gene encodes a T-type, low-voltage activated calcium channel. The T-type channels generate currents that are both transient, owing to fast inactivation, and tiny, owing to small conductance. T-type channels are thought to be involved in pacemaker activity, low-threshold calcium spikes, neuronal oscillations and resonance, and rebound burst firing. Many alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Sep 2011]

CACNA1G Gene-Disease associations (from GenCC):

• spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Illumina, PanelApp Australia, Ambry Genetics
• spinocerebellar ataxia type 42

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, Illumina
• intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1G	NM_018896.5	c.2301+3918A>G		intron_variant	Intron 9 of 37	ENST00000359106.10	NP_061496.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1G	ENST00000359106.10	c.2301+3918A>G		intron_variant	Intron 9 of 37	1	NM_018896.5	ENSP00000352011.5
CACNA1G	ENST00000507510.6	c.2301+3918A>G		intron_variant	Intron 9 of 36	1		ENSP00000423112.2

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87884 AN: 151884 Hom.: 26193 Cov.: 31

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.948

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.556

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.579 AC: 87970 AN: 152002 Hom.: 26232 Cov.: 31 AF XY: 0.583 AC XY: 43352 AN XY: 74306

African (AFR) AF: 0.633 AC: 26253 AN: 41448

American (AMR) AF: 0.571 AC: 8712 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1719 AN: 3468

East Asian (EAS) AF: 0.947 AC: 4900 AN: 5172

South Asian (SAS) AF: 0.695 AC: 3352 AN: 4820

European-Finnish (FIN) AF: 0.555 AC: 5870 AN: 10578

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.524 AC: 35571 AN: 67936

Other (OTH) AF: 0.561 AC: 1184 AN: 2112

Alfa AF: 0.551 Hom.: 36306

Bravo AF: 0.581

Asia WGS AF: 0.813 AC: 2824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.73
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs198555; hg19: chr17-48659843;